PPARγ ligands induce growth inhibition and apoptosis through p63 and p73 in hum an ovarian cancer cells
PPARγ ligands induce growth inhibition and apoptosis through p63 and p73 in hum an ovarian cancer cells
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DOI：
10.1016/j.bbrc.2011.02.052
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发表时间：
2011-03-18
影响因子：
3.1
通讯作者：
Heo, Dae Seog
中科院分区：
文献类型：
--
作者：
Kim, Soyeon;Lee, Jae-Jung;Heo, Dae Seog
过氧化物酶体增殖物激活受体 γ (PPAR γ) 激动剂，包括噻唑烷二酮类 (TZD)，可以诱导各种癌细胞类型的抗增殖、分化和凋亡。本研究探讨了 TZDs 对人类卵巢癌的抗癌作用机制。用 TZD 处理六种人卵巢癌细胞系（NIH：OVCAR3、SKOV3、SNU-251、SNU-8、SNU-840 和 2774），TZD 诱导细胞生长的剂量依赖性抑制。此外，蛋白质印迹显示这些细胞系表现出不同的 PPAR γ 蛋白表达水平。流式细胞术显示细胞周期停滞在 Cl 期，亚 G1 峰的出现证明了这一点。 TGZ 处理的细胞中 Bax、p21、PARP 和 cleaved caspase 3 水平升高的发现证实了这一观察结果。有趣的是，当我们确定 p53 诱导的生长抑制对这三种人类卵巢癌细胞的影响时，我们发现它们要么缺乏 p53，要么含有 p53 的突变形式。此外，TGZ 诱导内源性或外源性 p63 和 p73 蛋白的表达，并且 p63 或 p73 定向的短发夹 (si) RNA 抑制 TGZ 在这些细胞中调节 p21 表达的能力。因此，我们的结果表明，PPAR γ 配体可以诱导卵巢癌细胞的生长抑制并介导 p63 和 p73 表达，从而增强生长抑制和细胞凋亡。 PPAR γ 配体的肿瘤抑制作用可能可用于治疗卵巢癌。 (C) 2011 Elsevier Inc. 保留所有权利。
Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists, including thiazolidinediones (TZDs), can induce anti-proliferation, differentiation, and apoptosis in various cancer cell types. This study investigated the mechanism of the anticancer effect of TZDs on human ovarian cancer. Six human ovarian cancer cell lines (NIH:OVCAR3, SKOV3, SNU-251, SNU-8, SNU-840, and 2774) were treated with the TZD, which induced dose-dependent inhibition of cell growth. Additionally, these cell lines exhibited various expression levels of PPAR gamma protein as revealed by Western blotting. Flow cytometry showed that the cell cycle was arrested at the Cl phase, as demonstrated by the appearance of a sub-G1 peak. This observation was corroborated by the finding of increased levels of Bax, p21, PARP, and cleaved caspase 3 in TGZ-treated cells. Interestingly, when we determined the effect of p53-induced growth inhibition in these three human ovarian cancer cells, we found that they either lacked p53 or contained a mutant form of p53. Furthermore, TGZ induced the expression of endogenous or exogenous p63 and p73 proteins and p63- or p73-directed short hairpin (si) RNAs inhibited the ability of TGZ to regulate expression of p21 in these cells. Thus, our results suggest that PPAR gamma ligands can induce growth suppression of ovarian cancer cells and mediate p63 and p73 expression, leading to enhanced growth inhibition and apoptosis. The tumor suppressive effects of PPAR gamma ligands may have applications for the treatment of ovarian cancer. (C) 2011 Elsevier Inc. All rights reserved.